The Mutagenesis Core, under the supervision of Dr. S. John Mihic, Ph.D., will provide central resources to members of the Program Project. It will be the responsibility of the Mutagenesis Core to produce the glycine, GABAA and glutamate receptor subunit mutants required by the Harris Project for their expression studies. Initially these will be the specific mutants detailed in the Harris proposal. Later, as the modeling studies of Trudell and the structural studies of Overduin, progress, the Core will also make the mutations they require, to test specific hypotheses generated by their work. Beyond our use of traditional and established techniques of mutagenesis, we have developed and will use novel techniques allowing for the concurrent creation of multiple mutants of defined amino acids. The inclusion of a Mutagenesis Core in the Program Project will allow for a centralized facility to produce all of the mutants requested by the Harris Trudell and Overduin Projects in a timely, efficient and cost-effective manner.